A major objective of the proposed research is the study of the sequences of biochemical steps involved in the metabolism of ornithine and glutamate in the course of differentiation of several mammalian tissues. Enzymes of the urea cycle, the glutamate cycle and those involved in proline formation will be studied extensively. By correlating information on prominent biochemical patterns with the emergence of specific physiological functions at a given age, we hope to add a new dimension to our knowledge of growth and differentiation. Immediate as well as temporally removed responses of enzyme formation to hormonal stimuli will be studied in order to elucidate the roles of hormones in promoting, maintaining and perturbing biochemical balance in the developing organism. Tissue enzyme measurements and blood tests will be used to specify the abnormalities of rats that stop growing during the neonatal period and often die by the 15th day. The hypothesis that abnormal hormonal levels before or at birth may be responsible for the altered enzyme patterns in vital tissues is being tested. In the course of studies of the developmental formation or ornithine aminotransferase in liver and kidney, it has been determined that implantation of Walker tumors inhibited the normal developmental formation of ornithine aminotransferase in livers of the host but not in their kidneys. The effects of tumor bearing on the normal emergence of several liver enzymes have further been examined.